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Arthritis Res Ther. 2012 Feb 7;14(1):R29. doi: 10.1186/ar3732.

The neuropeptide neuromedin U promotes autoantibody-mediated arthritis.

Author information

  • 1Center for Immunology and Department of Pediatrics, University of Minnesota, Medical Biosciences Building, 2101 6th St SE Minneapolis, MN, 55414, USA.

Abstract

INTRODUCTION:

Neuromedin U (NMU) is a neuropeptide with pro-inflammatory activity. The primary goal of this study was to determine if NMU promotes autoantibody-induced arthritis. Additional studies addressed the cellular source of NMU and sought to define the NMU receptor responsible for its pro-inflammatory effects.

METHODS:

Serum containing arthritogenic autoantibodies from K/BxN mice was used to induce arthritis in mice genetically lacking NMU. Parallel experiments examined whether NMU deficiency impacted the early mast-cell-dependent vascular leak response induced by these autoantibodies. Bone-marrow chimeric mice were generated to determine whether pro-inflammatory NMU is derived from hematopoietic cells or stromal cells. Mice lacking the known NMU receptors singly and in combination were used to determine susceptibility to serum-transferred arthritis and in vitro cellular responses to NMU.

RESULTS:

NMU-deficient mice developed less severe arthritis than control mice. Vascular leak was not affected by NMU deficiency. NMU expression by bone-marrow-derived cells mediated the pro-arthritogenic effect. Deficiency of all of the known NMU receptors, however, had no impact on arthritis severity and did not affect the ability of NMU to stimulate intracellular calcium flux.

CONCLUSIONS:

NMU-deficient mice are protected from developing autoantibody-induced inflammatory arthritis. NMU derived from hematopoietic cells, not neurons, promotes the development of autoantibody-induced inflammatory arthritis. This effect is mediated by a receptor other than the currently known NMU receptors.

PMID:
22314006
[PubMed - indexed for MEDLINE]
PMCID:
PMC3392824
Free PMC Article
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